Project Title: “Biologic Discontinuation in Systemic JIA Predictors of Subsequent Disease Flare: A Cohort Study in the Childhood Arthritis and Rheumatology Research Alliance Registry”
Lay Summary: Systemic juvenile idiopathic arthritis (JIA) is distinct from the other types of JIA, characterized by daily fevers, rashes, joint swelling, and risk of macrophage activation syndrome (MAS), a rare but life-threatening complication. Treatments that block IL-1 and IL-6 (termed “biologics”) have been shown to be very effective. Now that a higher proportion of systemic JIA patients are achieving disease control, important questions have emerged surrounding 1) the optimal duration of biologic therapy, 2) drivers of biologic discontinuation, and 3) predictors of disease flare after biologic withdrawal. This study will leverage data within the systemic JIA cohort of the CARRA registry to address these knowledge gaps. Results will help inform treatment decisions and have important implications for patients with systemic JIA given the high cost of biologics, risk of medication-related adverse effects, burden of regular injections or infusions, and potential for life threatening disease flares.
Project Title: “Creation and Validation of a Modified Auto-inflammatory Disease Index (AIDAI) in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome”
Lay Summary: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common recurrent fever syndrome in children. Children with PFAPA have fevers that last 3-5 days and recur every 3-6 weeks, in the presence of the symptoms listed in the disease name. Although many different therapies are used to treat PFAPA, it is difficult to compare them because there are no reliable tests to measure disease activity. A disease activity index is a scoring system that accounts for different signs and symptoms of a disease to determine how severe it is. The goal of this study is to modify an already established Auto-Inflammatory Diseases Activity Index (AIDAI) and validate it to be used as an activity measure for PFAPA. This would be helpful to physicians because they would be able to treat children on a more individual level.
Project Title: “Association between UV Index and Disease Flare in Pediatric SLE Patients”
Lay Summary: Systemic lupus erythematosus (SLE) is a chronic, multi-organ autoimmune disease that can occur during childhood. Rash is one of the most common signs of active disease in lupus, and can range from mild to very severe and disfiguring. Although UV radiation is widely thought to be a trigger of SLE flare, studies evaluating the relationship between sun exposure and disease activity are contradictory. This study proposes to evaluate the relationship between sun exposure (using UV index) and presence of both SLE associated rash and overall disease activity. We will also examine the impact SLE rash has on patients’ overall quality of life. Increased understanding of the impact of this ubiquitous risk factor on pediatric SLE patients will enable us to better advise patients on protective practices and better control disease.
Project Title: “Mental Health Screening in Juvenile Myositis: Pilot and Feasibility Study”
Lay Summary: Juvenile myositis (JM) causes severe weakness and disfiguring skin rashes. JM symptoms and side effects of treatment can worsen quality of life for youth with JM and their families. Despite the effects that JM can have on quality of life, little is known about mental health in JM. Studies suggest that depression, anxiety, and other mental health issues are common in children with chronic conditions. This study will first assess the feasibility of mental health screening in a JM Center of Excellence. The study will also evaluate the relationship of mental health with indicators of physical health in JM. The study will also assess how mental health affects behaviors that are important for overall health maintenance, such as taking medications, staying physically active, and protecting against sun exposure. Future studies will build on these findings with the goal of improving mental and physical health in youth with JM.
Project Title: “Hydroxychloroquine Dosing and Pharmacokinetics in Pediatric Lupus”
Lay Summary: Active systemic lupus in children can result in long-term organ damage and disability. Hydroxychloroquine is a medication that improves disease activity in lupus and may help prevent long-term complications; however, the ideal dose of this medication in children is unknown. We propose to develop an optimal dosing strategy for hydroxychloroquine to improve the health of children who have systemic lupus.
Project Title: “Eliciting Perspectives of Adolescents and Young Adults with Pediatric Rheumatic Conditions around the Implementation of Healthcare Transition”
Lay Summary: In adolescence and early adulthood, rheumatology patients are required to become independent in managing their disease, health, and well-being, and navigating the healthcare system. Although healthcare providers recognize this as a crucial time to consistently monitor patients, there are still significant gaps in how healthcare empowers them to develop these skills. The purpose of this study is to learn about adolescents’ and young adults’ experiences transitioning from pediatric to adult rheumatology settings, and to obtain their concrete recommendations on how to improve upon this process. To do so, we will combine results from focus groups and a nationwide survey that asks participants questions about how they relate to and interpret the Six Core Elements of Healthcare Transition™, a model for improving transitional care in local healthcare settings. Our goal is that these results will be used to deliver more developmentally-tailored, patient-centered care to this at-risk population.
Project Title: “Patient Stratification through Muscular Immune Phenotyping in Psoriasis and Psoriatic JIA”
Lay Summary: Psoriasis is an inflammatory skin disease that can be associated with joint inflammation (arthritis). Childhood psoriasis is frequently more severe when compared to adult-onset disease. Studies in adults suggest that psoriasis is caused by activated immune cells that cause damage. However, disease mechanisms, treatment response and outcomes are largely unstudied in children. The involvement of immune cells in psoriasis has been established. Determining types and numbers of immune cells may allow early diagnosis and the prediction of the development of arthritis. Patterns identified in this study may allow a personalized approach to treatment. Using modern single cell imaging technology, this study aims to investigate immune cells in controls and patients to understand disease mechanisms and deliver markers of individual outcomes, such as the development of arthritis. Understanding the composition and characteristics of immune cells in psoriasis will result in predictors of disease outcomes and new individualized treatments.
Project Title: “Serious Infectious Complications Associated with Rituximab use in Children with Rheumatic Diseases”
Lay Summary: Although rituximab is increasingly used off-label for the treatment of pediatric rheumatic diseases, there remains a paucity of published data evaluating the potential adverse effects of rituximab in children. Several case studies and retrospective case series reported an increased risk of serious infections following rituximab treatment in children, including cases of death from infections. However, questions remain as to whether infections in these children were caused by rituximab and not the underlying disease or concomitant treatments, and whether closer immunologic surveillance of children undergoing treatment may be warranted. Here, we seek to better understand the risk and predictors of serious infectious complications following rituximab treatment in pediatric rheumatic diseases. A further goal is to identify gaps in immunologic monitoring for children receiving rituximab for a rheumatic disease. Findings from our study will create an evidence base for developing standardized practice guidelines that would benefit the prescribing and patient communities.
Project Title: “Feasibility and Reliability of Handheld 3D Photogrammetry for Imaging Linear Scleroderma of the Head”
Lay Summary: Linear scleroderma of the head is an uncommon autoimmune skin disease with significant medical and cosmetic impacts on children. Monitoring disease progression, defined as thinning of skin tissues, is difficult since accurate assessment requires significant clinical experience and hands-on time with patients. Non-invasive 3D cameras provide a finer assessment of skin changes, though stationary models are cumbersome and expensive. New handheld 3D cameras may potentially provide accurate monitoring of disease status across multiple clinical sites and providers, regardless of expertise. This pilot study will examine the feasibility and reliability of a low-cost commercially available handheld 3D facial camera compared with an established clinic-based stationary 3D camera system in accurately analyzing and characterizing pediatric scleroderma lesions. If this study is successful, handheld 3D cameras will give patients better access to scleroderma experts, eliminate unnecessary travel, and provide an objective measure of skin changes to assist treatment decisions and clinical trials.
Project Title: “Evaluating Care and Outcomes in Childhood-Onset Systemic Lupus Erythematosus”
Lay Summary: Systemic lupus erythematosus, or lupus, is a chronic condition that can cause inflammation in multiple organ systems. When lupus is diagnosed in childhood before 18 years of age, there is more risk for long-term complications. Inflammation in the kidneys, called lupus nephritis, is one of the subtypes of lupus with the most risk for permanent damage. This project will study the short-term outcomes for people who are diagnosed with lupus nephritis in childhood. First, we will look at the data that has been collected from patients with lupus nephritis in the CARRA Registry. Then, we will compare how the kidneys respond to different types of medicines. Finally, we will test if there are differences in outcomes based on demographics of the patients. This research will help pediatric rheumatologists better understand how to prevent long term damage for children with lupus.
Project Title: “Comprehensive Assessment of Viral Exposures in JIA patients”
Lay Summary: Arthritis in children most commonly begins before the age of 6 years, often seeming to appear out of the blue. Seasonal variation in onset and other clues have long suggested that the disease is triggered by viral infection, but there are so many different viruses that this hypothesis has been difficult to test. Here we will employ a next-generation DNA sequencing-based method term VirScan to evaluate past exposure to over 200 viruses in almost 100 young children with new-onset arthritis from two sites within the CARRA network, in comparison with a similar number of healthy children matched for age, gender, and geographic location. We predict that we will find important differences in the types and number of viral infections that these children have experienced, potentially pointing the way to new options for treatment and even prevention of juvenile idiopathic arthritis.
Project Title: "A Prospective Observational Study Comparing the Non-inferiority of Mycophenolate Mofetil to Methotrexate for the Treatment of Juvenile Localized Scleroderma"
Lay Summary: Juvenile Localized Scleroderma (jLS) is an inflammatory disease affecting the skin and other organs of children, caused by an impaired function of their immune system. It can be associated with body disfigurement and disability due to growth disturbance. Standard treatment for jLS includes the use of medications that control the excessive inflammation to prevent irreversible damage. The most widely used treatment regimen include methotrexate (MTX), either alone or in combination with corticosteroids. While many respond to this regimen, at least 25% of patients do not tolerate or fail to respond to MTX. A few studies have showed improvement of disease in patients with severe LS that were treated with mycophenolate mofetil (MMF). However, the evidence for its use is limited. In this study, we intend to investigate how effective MMF is in treating jLS as compared to MTX, with the goal to improve the outcome of these patients.
Project Title: "Using Biomarkers to Predict Response to Abatacept in Oligo JIA"
Lay Summary: Children with oligoarticular juvenile idiopathic arthritis initially present with only a few arthritis joints (less than 5). Some children with oligo JIA will continue to have mild disease (oligoarticular course) and others will go onto develop more severe disease with more arthritic joints (polyarticular course) and eye inflammation (uveitis). As pediatric rheumatologists, we would like to use biomarkers from the peripheral blood to identify which patients are at greatest risk for severe disease. If we can identify at risk patients, we can try to prevent disease extension with medications. This study will allow us to collect and analyze blood samples from oligo JIA patients in an effort to answer these questions.
Project Title: "Exosomes and Immune Modulation in Pediatric SLE"
Lay Summary: Pediatric lupus is an autoimmune disorder with diverse clinical presentations, affecting multiple organ systems. The clinical heterogeneity is a reflection of the underlying dysregulated immune system, which is still poorly understood. The goal of this proposal is to elucidate ht mechanisms that govern immune derangements in pediatric lupus, which would provide the foundation for selective therapeutic interventions. To achieve this goal, this study will dissect the role of circulating serum particle sin initiating inflammation in lupus. Exosomes are cell-derived small particles present in multiple bodily fluids including serum. Exosomes contain proteins and nucleic material that can modulate the function other cells . This study wll compare the cellular origin and composition of exosomes from lupus patients' serum versus healthy control serum; and how the exosomes affect surrounding immune cells. This comparison will identify key differences between lupus and health control serum exosomes, which can be used to identify novel therapeutic targets.
Project Title: "Clinical and Functional Significance of JIA-Specific Risk Alleles"
Lay Summary: This project is an important first step in our ability to use genetic information to guide how we monitor and treat juvenile idiopathic arthritis. In this study, we will examine three genetic variants associated with JIA and whose biological effects we have characterized. We will determine whether these genetic variants are associated with particular clinical features in JIA. If we are successful, this project will be the start of an ambitious second phase aimed to link genetic information to patient outcomes across the CARRA network.
Project Title: “Adverse Childhood Experiences in Youth with Juvenile Idiopathic Arthritis”
Lay Summary: Adverse Childhood Experiences (ACEs) are major stressors such as abuse, parental incarceration, and hunger. Almost half of children in the United States have experienced at least 1 ACE. ACEs are associated with chronic illness in childhood and adulthood. Studies show that ACEs are associated with worse disease outcomes among adults with rheumatologic diseases, but there have not yet been any studies of the effect of ACEs on children with rheumatologic diseases. The first part of this study will assess how to best screen for ACEs among children with juvenile idiopathic arthritis, with the goal of making sure that complete information is obtained in a way that is comfortable for families. The second part of this study will assess whether ACEs are associated with worse disease activity, pain, physical function, and quality of life in children and teenagers with juvenile idiopathic arthritis.
Project Title: “Procalcitonin and Calprotectin for Differentiation of Infection and Disease Flare in Systemic Juvenile Idiopathic Arthritis”
Lay Summary: Juvenile idiopathic arthritis is a common pediatric rheumatologic disease, and the mainstay of treatment is immunosuppressive medication. The most problematic complication of immunosuppression is infection. Distinguishing the inflammation of immune flates with that of infections can be very challenging, particularly in systemic JIA (sJIA), where signs and symptoms are similar. In this study, we propose using two markers in the blood, procalcitonin and calprotectin, to distinguish disease flare and infection in children with sJIA. In order to achive this, we will draw blood from children with sJIA at two timepoints, when blood is being drawn anyway as part of standard of care. We anticipate that procalcitonin will be elevated in children with infection, and calprotectin will be leevated in children with disease flare, so that the combination of these two markers will give very valuable information together. This will allow more accurate and early diagnosis to direct proper treatment.